Smoking remains a leading cause of preventable disease and premature death woridwide. Approximately 1 out of every 5 deaths is associated with cigarette smoking, and roughly half of all daily smokers will die prematurely from tobacco-related illnesses. Nicotine is widely accepted as a necessary constituent in tobacco driving use and dependence. A significant reduction in the nicotine content of cigarettes represents an innovative regulatory strategy with the potential to markedly reduce consumption and lead to greater likelihood of quitting. The Family Smoking Prevention and Tobacco Control Act (FSPTCA) enables the FDA to establish tobacco product standards including placing limits on the allowable nicotine content of cigarettes. For such a policy to be implemented safely and successfully, a number of critical issues and questions must be evaluated. One primary issue is to determine an appropriately low yield of nicotine content per cigarette that is below the addictive 'threshold' of nicotine, while at the same time balances reduced withdrawal effects and maximizes acceptability. Study 1 directly bears on this issue. Study 1 will assess three different low nicotine yields (0.02, 0.06, 0.18 mg) over a 6-week period and the data generated will be used to select an optimal nicotine yield for the remaining study in Project 1 and for Projects 2 and 3. A second major issue is whether simultaneous nicotine replacement therapy (NRT) facilitates the transition to very low nicotine content (VLNC) cigarettes. Recent evidence suggests that NRT may decrease use of VLNC cigarettes, reduce the volume of smoke inhaled per cigarette, and reduce drop-out rate. Study 2 will compare the effects of VLNC cigarettes in participants on 21 mg transdermal nicotine to another group that smokers VLNC cigarettes while wearing a placebo patch. A third group smoking normal nicotine content cigarettes and wearing placebo patches will be included as an additional control. RELEVANCE (See instructions): This project has two goals. Study 1 will determine the optimal yield for very low nicotine cigarettes that leads to reduced smoking, but also minimal discomfort and maximal acceptability. Study 2 will determine if nicotine replacement aids in the transition to very low nicotine cigarettes. Both studies will advance understanding of the feasibility of using very low nicotine cigarettes to reduce the health burden of smoking.